News

A new genome-wide association study (GWAS) investigated the genetics of educational attainment in over 1 million individuals, including 2,000 from the Berlin Aging Study II (BASE-II) contributed by our group. The study represents one of the largest GWAS ever performed to date and identified nearly 1,300 independent lead SNPs to show genome-wide significant association with education. Many of the identified variants are located in genes involved in brain-development processes and neuron-to-neuron communication. Polygenic analyses suggest that up to 13% of the variance underlying inter-individual differences in educational attainment can now be explained by these data, more than explained by household income but less than by parental educational attainment. The study was published in the journal Nature Genetics.

Researchers from LIGA together with two colleagues from the Institute of Neurogenetics this month published the first ever field synopsis for genetic association studies in dystonia. The study, led by LIGA PhD student Olena Ohlei, aimed at separating the wheat from the chaff for genetic association results in datasets of isolated dystonia. To this end, we scrutinized more than 3,500 published articles resulting in the inclusion of 42 independent publications allowing 134 meta-analyses on 45 variants across 17 genes. While subsequently performed meta-analyses pinpointed several association signals with variants in TOR1A, DRD1, and ARSG, no single variant displayed compelling association with dystonia in the available data highlighting the need for additional large-scale studies. The publication was part of an ongoing DFG-funded project led by Lars Bertram and Jeanette Erdmann at the Institute of Cardiogenetics. The Ohlei et al paper is now published in the Journal Parkinsonism and Related Disorders (after having been posted on bioRxiv prior to peer-review).

Much like many other human phenotypes, cognitive function is a highly polygenic trait. In the largest genome-wide association study (GWAS) performed to date, our colleagues Gail Davies and Ian Deary at University of Edinburgh spearheaded analyses on over 300,000 individuals (including ~2000 from the Berlin Aging Study II, co-led by LIGA investigators) identifying nearly 150 independent genetic loci associated with cognitive function, many of which had not been known previously. Within the novel genetic loci are DNA variants associated with neurodevelopmental and neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diesease), physical and psychiatric illnesses, and brain structure. The results of this study shed important new light on the inborn factors contributing to cognitive (dys-)function in humans. The study was published in the journal Nature Communications.

The aim of this study was to identify microRNAs that show consistent differential expression across all published expression studies in Parkinson’s disease (PD). To this end, we performed a systematic literature search on microRNA expression studies in PD and meta-analyzed the extracted data. We identified several microRNAs that showed highly significant differential expression in PD blood and brain. Future studies need to assess the possible role of these miRNAs in PD pathogenesis and progression as well as the utility as biomarkers for diagnosis, progression or prediction of PD. The study was published as pre-print on bioRxiv.

Elucidating factors that influence human longevity is of great interest to a number of disciplines in medicine and biology. In this study, LIGA contributed genome-wide data from the Berlin Aging Study II to a meta-analysis using parental life span in >600000 individuals as outcome measure. We identified associations at HLA-DQA/DRB1 and LPA and found that genetic variants that increase educational attainment positively affects lifespan whereas increasing BMI showed negative effects. The study was published in the journal Nature Communications.

This work represents the first bona-fide genome-wide association study (GWAS) assessing reproductive behavior in humans, to which LIGA contributed the data from the Berlin Aging Study II. Overall, nearly 350,000 individuals were analyzed leading to the identification of 16 independent loci that are significantly associated with ‘age at first birth’ and/or ‘number of children ever born’. These identified loci harbor genes that are likely to have a role,in human reproduction and infertility. The study was published in the journal Nature Genetics.